Secretome analysis of ionizing radiation-induced senescent cancer cells reveals that secreted RKIP plays a critical role in neighboring cell migration

Na Kyung Han, Bong Cho Kim, Hyung Chul Lee, Yoon Jin Lee, Myung Jin Park, Sung-Gil Chi, Young-Gyu Ko, Jae Seon Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cellular senescence is a physiological program of irreversible growth arrest that is considered to play an important role in tumor suppression. Recent studies demonstrated that senescent cells secrete multiple growth regulatory proteins that could alter the behavior of neighboring cells. In this study, we investigated the effect of secretory proteins from ionizing radiation (IR) induced senescent tumor cells on normal and tumor cells. Conditioned medium (CM) from IR-induced senescent MCF7 cells significantly increased cell proliferation, invasion, migration, and wound healing activity in MCF7 cells and HUVECs. Comparative proteomics analysis revealed 24 differentially secreted protein spots including Raf kinase inhibitor protein (RKIP), α-Enolase, AKAP9, and MARK4, and the findings were confirmed by Western blot analysis of IR-induced senescent cancer cells. We found that RKIP was secreted via the classical pathway, and the transfection of small interfering RNA against RKIP suppressed CM-induced migration in MCF7 cells. Treatment with recombinant human RKIP increased the migratory activity of MCF7 cells. Taken together, our results demonstrate that the senescence-associated secretory protein RKIP could be the principal target to prevent the potential effects of the secretome from IR-induced senescent tumor cells on neighboring cell migration.

Original languageEnglish
Pages (from-to)2822-2832
Number of pages11
JournalProteomics
Volume12
Issue number18
DOIs
Publication statusPublished - 2012 Sep 1

Keywords

  • Biomedicine
  • Cellular senescence
  • Ionizing radiation
  • RKIP
  • Secretome
  • Tumor cells

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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